Sternohyoid and diaphragm muscle form and function during postnatal development in the rat

Abstract

New findings r What is the central question of this study?Co-ordinated activity of the thoracic pump and pharyngeal dilator muscles is critical for maintaining airway calibre and respiratory homeostasis. Whilst postnatal maturation of the diaphragm has been well characterized, surprisingly little is known about the developmental programme in the airway dilator muscles. r What is the main finding and its importance?Developmental increases in force-generating capacity and fatigue in the sternohyoid and diaphragm muscles are attributed to a maturational shift in muscle myosin heavy chain phenotype. This maturation is accelerated in the sternohyoid muscle relative to the diaphragm and may have implications for the control of airway calibre in vivo.The striated muscles of breathing, including the thoracic pump and pharyngeal dilator muscles, play a critical role in maintaining respiratory homeostasis. Whilst postnatal maturation of the diaphragm has been well characterized, surprisingly little is known about the developmental programme in airway dilator muscles given that co-ordinated activity of both sets of muscles is needed for the maintenance of airway calibre and effective pulmonary ventilation. The form and function of sternohyoid and diaphragm muscles from Wistar rat pups [postnatal day (PD) 10, 20 and 30] was determined. Isometric contractile and endurance properties were examined in tissue baths containing Krebs solution at 35• C. Myosin heavy chain (MHC) isoform composition was determined using immunofluorescence. Muscle oxidative and glycolytic capacity was assessed by measuring the activities of succinate dehydrogenase and glycerol-3-phosphate dehydrogenase using semi-quantitative histochemistry. Sternohyoid and diaphragm peak isometric force and fatigue increased significantly with postnatal maturation. Developmental myosin disappeared by PD20, whereas MHC 2B areal density increased significantly from PD10 to PD30, emerging earlier and to a much greater extent in the sternohyoid muscle. The numerical density of fibres expressing MHC 2X and MHC 2B increased significantly during development in the sternohyoid. Diaphragm succinate dehydrogenase activity and sternohyoid glycerol-3-phosphate dehydrogenase activity increased significantly with age. Developmental increases in force-generating capacity and fatigue in the sternohyoid and diaphragm muscles are attributed to a postnatal shift in muscle MHC phenotype. The accelerated maturation of the sternohyoid muscle relative to the diaphragm may have implications for the control of airway calibre in vivo.

Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic intermittent hypoxia

“…; O'Connell et al . ). We found no change in SDH or GPDH activity, suggesting that an alteration in metabolic enzymes is not likely to be responsible for increased diaphragm fatigue observed in our model.…”

Respiratory muscle dysfunction in animal models of hypoxic disease: antioxidant therapy goes from strength to strength

“…Notwithstanding the essential function of respiratory muscles to sustain life, the pump and airway dilator striated muscles of breathing retain considerable capacity for structural and functional plasticity in response to changes in functional demands. This extends far beyond developmental periods wherein temporal fiber-type and functional changes are well recognized 13–17. Indeed, diaphragm and upper airway dilator muscles show remarkable capacity for plasticity, as impressive as that documented in limb skeletal muscles in response to a variety of stressors in health and disease 18…”

“…Indeed, neonatal exposure to CIH primes increased susceptibility to subsequent hypoxic stress in later life 15. Unlike airway dilator muscle responses,15,17 exposure to CIH (FiO 2 =5% at nadir; 12 cycles per hour; 8 hours per day) has no discernible effect on diaphragm form or function,16 an outcome that may relate to intrinsic differences in upper airway and diaphragm muscle fiber type and metabolic programming during development 13–17…”

Theβ2‐adrenoceptor agonist terbutaline recovers rat pharyngeal dilator muscle force decline during severe hypoxia

“…Five minutes after the force-frequency protocol, repeated muscle contraction was induced by stimulation at 40 Hz with 300 ms trains every 2 s for a period of 2 min to produce isometric fatigue. This low-frequency fatigue protocol has been widely used and previously documented in studies of rat sternohyoid (O'Halloran, 2006;Dunleavy et al, 2008;Skelly et al, 2010Skelly et al, , 2012McMorrow et al, 2011;O'Connell et al, 2013). Studies were performed in control conditions (hyperoxia) AE terbutaline (1 lM).…”

“…The sternohyoid is easily accessible and has fibres running longitudinally, making it a suitable muscle for ex vivo study of contractile properties. Also, we have characterized rat sternohyoid muscle contractile and endurance properties in several previous studies (O'Halloran, 2006;Dunleavy et al, 2008;Skelly et al, 2010Skelly et al, , 2012McMorrow et al, 2011;O'Connell et al, 2013). To ascertain whether the effects of terbutaline were mediated via b-ARs, we investigated whether propranolol blocked the effects of terbutaline.…”